title: MDR1 is related to intestinal epithelial injury induced by acetylsalicylic acid.
abstract: OBJECTIVE
  Although the cytotoxicity of aspirin against the intestinal epithelium is a major clinical problem, little is known about its pathogenesis. We assessed the involvement of Multi Drug Resistance (MDR) 1 in intestinal epithelial cell injury caused by aspirin using MDR1 gene-transfected Caco2 cells.
  
  
  METHODS
  Caco2 cells were treated with various concentrations of aspirin for 24 h. After treatment of Caco2 cells with verapamil, a specific inhibitor of MDR1, we assessed the extent of cell injury using a WST-8 assay at 24 h after aspirin-stimulation. We performed the same procedure in MDR1 gene-transfected Caco2 cells. To determine the function of MDR1 in the metabolism of aspirin, flux study was performed using (14)C-labeled aspirin.
  
  
  RESULTS
  The level of aspirin-induced cell injury was higher in verapamil-treated Caco2 cells than in control cells and was less serious in MDR1-transfected Caco2 cells than in control vector-transfected cells. The efflux of (14)C-labeled aspirin was higher in verapamil-treated Caco2 cells than in control cells.
  
  
  CONCLUSIONS
  These data suggest that aspirin effux occurs through the MDR1 transporter and that the MDR1 transporter is involved in the pathogenesis of aspirin-induced cell injury.
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Kugai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoriki
authors.forename: Akifumi
authors.initials: A
authors.lastname: Fukui
authors.forename: Ying
authors.initials: Y
authors.lastname: Qin
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Higashimura
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.forename: Naohisa
authors.initials: N
authors.lastname: Yoshida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kamada
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Konishi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yagi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shirasaka
authors.forename: Ikumi
authors.initials: I
authors.lastname: Tamai
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology*; D015153:Blotting, Western; D018938:Caco-2 Cells; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D001241:Aspirin